Cellular and serological responses to vaccination in chronic kidney disease

Abstract

Chronic kidney disease (CKD) and haemodialysis (HD) are associated with an increased risk of hepatitis B infection due to exposure to the virus during haemodialysis, in conjunction with impaired seroconversion to hepatitis B vaccination (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the cellular defects responsible for impaired vaccine immunity observed in CKD and HD have not yet been identified. This project studied serological and cellular responses to HBV in CKD and HD to identify defects in vaccine-induced cellular responses that could account for impaired seroconversion and clarify the effects of an augmented vaccine dose schedule. These results were compared with responses to seasonal influenza vaccination. There was a clear benefit in rates and magnitude of seroconversion after an augmented 40mcg HBV dose schedule in CKD. This permitted comparison of responders and non-responders. Serological non-responders with CKD exhibited a reduction in CXCR3+CCR6- CXCR5+ memory T cells at baseline. Seasonal influenza vaccine elicited a plasmablast (PB) response in both healthy controls and CKD, but HBV elicited a poor plasmablast response in both groups. Both vaccinations induced activation of the CXCR3+CCR6- subset of circulating T follicular helper cells (cTFH) in healthy controls, and but this response was impaired in CKD after HBV, even with the augmented 40mcg HBV dose schedule, and appears not to be reversed by haemodialysis. Despite this, some patients receiving haemodialysis generate detectable post-vaccination HBsAb, and this correlates with activation within the CXCR3+CCR6- cTFH compartment. We concluded that cellular responses to seasonal influenza vaccine are preserved in CKD and haemodialysis. However, CKD confers a specific defect in cTFH activation that contributes to the impaired seroconversion to HBV, and this defect persists despite renal replacement therapy with haemodialysis.